Abstract:
:Laboratory models, including animal tissues and live animals, have proven useful for discovery of molecular targets of alcohol action as well as for characterization of genetic and environmental factors that influence alcohol's neural actions. Here we consider strengths and weaknesses of laboratory models used in alcohol research and analyze the limitations of using animals to model a complex human disease. We describe targets for the neural actions of alcohol, and we review studies in which animal models were used to examine excessive alcohol drinking and to discover genes that may contribute to risk for alcoholism. Despite some limitations of the laboratory models used in alcohol research, these experimental approaches are likely to contribute to the development of new therapies for alcohol abuse and alcoholism.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Lovinger DM,Crabbe JCdoi
10.1038/nn1581subject
Has Abstractpub_date
2005-11-01 00:00:00pages
1471-80issue
11eissn
1097-6256issn
1546-1726pii
nn1581journal_volume
8pub_type
杂志文章,评审abstract::Grid cells in layer II of the medial entorhinal cortex form a principal component of the mammalian neural representation of space. The firing pattern of a single grid cell has been hypothesized to be generated through attractor dynamics in a network with a specific local connectivity including both excitatory and inhi...
journal_title:Nature neuroscience
pub_type: 杂志文章
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abstract::Precise apposition of pre- to postsynaptic specializations is required for optimal function of chemical synapses, but little is known about how it is achieved. At the skeletal neuromuscular junction, active zones (transmitter release sites) in the nerve terminal lie directly opposite junctional folds in the postsynapt...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/88414
更新日期:2001-06-01 00:00:00
abstract::Humans have ~400 intact odorant receptors, but each individual has a unique set of genetic variations that lead to variation in olfactory perception. We used a heterologous assay to determine how often genetic polymorphisms in odorant receptors alter receptor function. We identified agonists for 18 odorant receptors a...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3598
更新日期:2014-01-01 00:00:00
abstract::The CNS, which consists of the brain and spinal cord, is continuously monitored by resident microglia and blood-borne immune cells such as macrophages, dendritic cells and T cells to detect for damaging agents that would disrupt homeostasis and optimal functioning of these vital organs. Further, the CNS must balance b...
journal_title:Nature neuroscience
pub_type: 杂志文章,评审
doi:10.1038/nn.3161
更新日期:2012-07-26 00:00:00
abstract::Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants, but the mechanisms by which they influence behavior are only partially resolved. Adult hippocampal neurogenesis is necessary for some of the responses to SSRIs, but it is not known whether mature dentate gyrus granule cells (DG GCs) also ...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.4116
更新日期:2015-11-01 00:00:00
abstract::Chronic morphine exposure upregulates adenylate cyclase signaling and reduces analgesic efficacy, a condition known as opioid tolerance. Nonopioid neurotransmitters can enhance morphine tolerance, but the mechanism for this is poorly understood. We show that morphine tolerance was delayed in mice lacking vasopressin 1...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/s41593-018-0144-y
更新日期:2018-06-01 00:00:00
abstract::The US government is re-examining how it funds science, but it remains to be seen whether the administration can overcome tradition and bureaucratic inertia and achieve a substantial renovation of the grants peer-review system. ...
journal_title:Nature neuroscience
pub_type: 社论
doi:10.1038/nn0208-119
更新日期:2008-02-01 00:00:00
abstract::The growth of neurites (axon and dendrite) should be appropriately regulated by their interactions in the development of nervous systems where a myriad of neurons and their neurites are tightly packed. We show here that mammalian seven-pass transmembrane cadherins Celsr2 and Celsr3 are activated by their homophilic in...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1933
更新日期:2007-08-01 00:00:00
abstract::To define the role of the Raf serine/threonine kinases in nervous system development, we conditionally targeted B-Raf and C-Raf, two of the three known mammalian Raf homologs, using a mouse line expressing Cre recombinase driven by a nestin promoter. Targeting of B-Raf, but not C-Raf, markedly attenuated baseline phos...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1898
更新日期:2007-05-01 00:00:00
abstract::Entorhinal grid cells in mammals fire as a function of animal location, with spatially periodic response patterns. This nonlocal periodic representation of location, a local variable, is unlike other neural codes. There is no theoretical explanation for why such a code should exist. We examined how accurately the grid...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2901
更新日期:2011-09-11 00:00:00
abstract::Central pattern generators (CPGs) are spinal neuronal networks required for locomotion. Glutamatergic neurons have been implicated as being important for intrinsic rhythm generation in the CPG and for the command signal for initiating locomotion, although this has not been demonstrated directly. We used a newly genera...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2482
更新日期:2010-02-01 00:00:00
abstract::Glycine receptors (GlyRs), together with GABA(A) and nicotinic acetylcholine (ACh) receptors, form part of the ligand-activated ion channel superfamily and regulate the excitability of the mammalian brain stem and spinal cord. Here we report that the ability of the neurotransmitter glycine to gate recombinant and nati...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1095
更新日期:2003-08-01 00:00:00
abstract::Over the last 10 years, optogenetics has become widespread in neuroscience for the study of how specific cell types contribute to brain functions and brain disorder states. The full impact of optogenetics will emerge only when other toolsets mature, including neural connectivity and cell phenotyping tools and neural r...
journal_title:Nature neuroscience
pub_type: 评论,杂志文章
doi:10.1038/nn.4094
更新日期:2015-09-01 00:00:00
abstract::Calcium arising through release from intracellular stores and from influx across the plasma membrane is essential for signalling by specific guidance cues and by factors that inhibit axon regeneration. The mediators of calcium influx in these cases are largely unknown. Transient receptor potential channels (TRPCs) bel...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1459
更新日期:2005-06-01 00:00:00
abstract::A picture viewed from its center of projection generates the same retinal image as the original scene, so the viewer perceives the scene correctly. When a picture is viewed from other locations, the retinal image specifies a different scene, but we normally do not notice the changes. We investigated the mechanism unde...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1553
更新日期:2005-10-01 00:00:00
abstract::Over the past two centuries, prevalent models of energy and glucose homeostasis have emerged from careful anatomical descriptions in tandem with an understanding of cellular physiology. More recent technological advances have culminated in the identification of peripheral and central factors that influence neural circ...
journal_title:Nature neuroscience
pub_type: 杂志文章,评审
doi:10.1038/nn.3217
更新日期:2012-10-01 00:00:00
abstract::Fear-inducing memories can be state dependent, meaning that they can best be retrieved if the brain states at encoding and retrieval are similar. Restricted access to such memories can present a risk for psychiatric disorders and hamper their treatment. To better understand the mechanisms underlying state-dependent fe...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.4084
更新日期:2015-09-01 00:00:00
abstract::Tumor-associated macrophages (TAMs) play an important role in the immune response to cancer, but the mechanisms by which the tumor microenvironment controls TAMs and T cell immunity are not completely understood. Here we report that kynurenine produced by glioblastoma cells activates aryl hydrocarbon receptor (AHR) in...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/s41593-019-0370-y
更新日期:2019-05-01 00:00:00
abstract::All the higher mental and cognitive functions unique to humans depend on the neocortex ('new' cortex, referring to its relatively recent appearance in evolution), which is divided into discrete areas that subserve distinct functions, such as language, movement and sensation. With a few notable exceptions, all neocorti...
journal_title:Nature neuroscience
pub_type: 杂志文章,评审
doi:10.1038/nn752
更新日期:2001-11-01 00:00:00
abstract::Mammalian sterile 20-like kinase-3b (Mst3b, encoded by Stk24), regulates axon outgrowth in embryonic cortical neurons in culture, but its role in vivo and in neural repair is unknown. Here we show that Mst3b mediates the axon-promoting effects of trophic factors in mature rat retinal ganglion cells (RGCs) and dorsal r...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2414
更新日期:2009-11-01 00:00:00
abstract::The mechanistic target of rapamycin (mTOR) acts as a highly conserved signaling "hub" that integrates neuronal activity and a variety of synaptic inputs. mTOR is found in two functionally distinct complexes, mTORC1 and mTORC2, that crucially control long-term synaptic efficacy and memory storage. Dysregulation of mTOR...
journal_title:Nature neuroscience
pub_type: 杂志文章,评审
doi:10.1038/nn.3546
更新日期:2013-11-01 00:00:00
abstract::Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia (>99%) in adult mice. Previous studies reported that repopulated microglia were largely derived from microglial progenitor cells expressing nestin in the brain. However, the origin of these repopulated microglia has been ...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/s41593-018-0090-8
更新日期:2018-04-01 00:00:00
abstract::Dopaminergic (DA) signaling governs the control of complex behaviors, and its deregulation has been implicated in a wide range of diseases. Here we demonstrate that inactivation of the Fto gene, encoding a nucleic acid demethylase, impairs dopamine receptor type 2 (D2R) and type 3 (D3R) (collectively, 'D2-like recepto...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3449
更新日期:2013-08-01 00:00:00
abstract::Binocular competition is thought to drive eye-specific segregation in the developing visual system, potentially through Hebbian synaptic learning rules that are sensitive to correlations in afferent activity. Altering retinal activity can disrupt eye-specific segregation, but little is known about the temporal feature...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3007
更新日期:2011-11-18 00:00:00
abstract::The distinct electrical properties of axonal and dendritic membranes are largely a result of specific transport of vesicle-bound membrane proteins to each compartment. How this specificity arises is unclear because kinesin motors that transport vesicles cannot autonomously distinguish dendritically projecting microtub...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2318
更新日期:2009-05-01 00:00:00
abstract::Retinal bipolar cells have been assumed to generate purely graded responses to light. To test this idea we imaged the presynaptic calcium transient in live zebrafish. We found that ON, OFF, transient and sustained bipolar cells are all capable of generating fast 'all-or-none' calcium transients modulated by visual sti...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2841
更新日期:2011-06-26 00:00:00
abstract::Humans, and animals, often encounter ambiguous situations that require a decision on whether to take an offense or a defense strategy. Behavioral studies suggest that a strategy decision is frequently made before concrete options are evaluated. It remains enigmatic, however, how a strategy is determined without explor...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3999
更新日期:2015-05-01 00:00:00
abstract::Imaging, from magnetic resonance imaging (MRI) to localization of specific macromolecules by microscopies, has been one of the driving forces behind neuroinformatics efforts of the past decade. Many web-accessible resources have been created, ranging from simple data collections to highly structured databases. Althoug...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1229
更新日期:2004-05-01 00:00:00
abstract::Rapid progress has been made in understanding the synaptic changes required for memory encoding. Several companies are now attempting to use information about the induction and consolidation phases of this process to build memory-enhancing drugs. These efforts have produced novel compounds that improve retention score...
journal_title:Nature neuroscience
pub_type: 杂志文章,评审
doi:10.1038/nn935
更新日期:2002-11-01 00:00:00
abstract::We report two functional magnetic resonance imaging experiments showing enhanced responses in human middle superior temporal sulcus for angry relative to neutral prosody. This emotional enhancement was voice specific, unrelated to isolated acoustic amplitude or frequency cues in angry prosody, and distinct from any co...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1392
更新日期:2005-02-01 00:00:00